The applicant, Dr. Elad Ziv, is an associate professor of medicine at UCSF and leads a patient oriented research program that investigates genetic susceptibility to common cancers and hematological traits. A major focus of Dr. Ziv's program is the study of genetic factors underlying breast cancer susceptibility. As part of this proposal, Dr. Ziv will search for genetic factors underlying the association between mammographic breast density and breast cancer risk. Mammographic breast density is known to be a strong risk factor for breast cancer and is also a highly heritable trait. Dr. Ziv will analyze a large genome wide association study (GWAS) that his group is generating, comparing 500 women from the top quintile of age and BMI-adjusted breast density to 500 women from the bottom quintile. He will perform a replication analysis of the top 1500 variants in a replication dataset of another 500 women from the top and 500 women from the bottom quintile of age and BMI adjusted density. In addition, his group will search for genetic variants that are associated with both breast densit and breast cancer risk. They will perform a combined analysis of breast density and breast cancer GWAS datasets, using GWAS datasets of breast cancer susceptibility that his group has generated and a publicly available breast cancer GWAS datasets. Dr. Ziv and colleagues will also use next generation sequencing to search for rare variants that may explain the overlap between these traits. In particular, women with a strong family history of breast cancer who are also in the top quintile of age and BMI-adjusted breast density will be selected for whole exome sequencing. As part of this proposal, Dr. Ziv will expand his capacity to mentor junior investigators and develop additional skills to maximize his potential as a mentor. Dr. Ziv has mentored over 15 junior faculty members, fellows, residents and students. He is affiliated with 3 T32 programs for mentoring fellows. As part of this proposal, Dr. Ziv will take on additional mentees at the post-doctoral level and continue to mentor the junior faculty, fellows currently working with him. He will also pursue additional training that will enhance his mentoring and scientific skills. PUBLIC HEALTH RELEVANCE: This proposal will search for genetic variants that underlie the association between breast density and breast cancer risk. Breast density is known to be a strong risk factor for breast cancer. The applicant will also use this proposal to continue and enhance his role as a mentor to junior investigators pursuing patient oriented research, studying genetic and environmental factors that underlie cancer susceptibility.